RT Journal Article
SR Electronic
T1 Adiponectin Promotes Maternal β-Cell Expansion Through Placental Lactogen Expression
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP db200471
DO 10.2337/db20-0471
A1 Qiao, Liping
A1 Saget, Sarah
A1 Lu, Cindy
A1 Hay, William W.
A1 Karsenty, Gerard
A1 Shao, Jianhua
YR 2020
UL http://diabetes.diabetesjournals.org/content/early/2020/10/21/db20-0471.abstract
AB Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM). Our previous study reported that adiponectin gene knockout mice (Adipoq-/-) develop GDM due to insulin insufficiency. The main objective of this study was to elucidate the underlying mechanism through which adiponectin controls islet expansion during pregnancy. A significant reduction in β-cell proliferation rates, β-cell areas, and blood insulin concentrations was detected in Adipoq-/- mice at mid-pregnancy. Surprisingly, conditionally knocking down adiponectin receptor 1 (AdipoR1) or AdipoR2 genes in β-cells during pregnancy did not reduce β-cell proliferation rates or blood insulin concentrations. In vitro adiponectin treatment also failed to show any effect on β-cell proliferation of isolated pancreatic islets. It was reported that placental lactogen (PL) plays a crucial role in pregnancy-induced maternal β-cell proliferation. A significant decrease in phosphorylation of signal transducer and activator of transcription 5, a downstream molecule of PL signaling, was observed in islets from Adipoq-/- dams. The mRNA levels of mouse PL genes were robustly decreased in the placentas of Adipoq-/- dams. In contrast, adiponectin treatment increased PL expression in human placenta explants and JEG3 trophoblast cells. Most importantly, bovine PL injection restored β-cell proliferation and blood insulin concentrations in Adipoq-/- dams. Together, these results demonstrate that adiponectin plays a vital role in pregnancy-induced β-cell proliferation by promoting PL expression in trophoblast cells.